Atezolizumab And Bevacizumab In Treating Patients With Rare Solid Tumors

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-02-22	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-24
First Submitted that Met QC Criteria 2017-03-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-27
First Posted (ACTUAL) 2017-03-08	Results First Posted N/A	Last Verified 2025-04

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (atezolizumab, bevacizumab) Patients receive atezolizumab and bevacizumab IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	DRUG: Atezolizumab Given IV BIOLOGICAL: Bevacizumab Given IV OTHER: Laboratory Biomarker Analysis Correlative studies OTHER: Pharmacological Study Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (atezolizumab, bevacizumab)

Patients receive atezolizumab and bevacizumab IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

DRUG: Atezolizumab

Given IV

BIOLOGICAL: Bevacizumab

Given IV

OTHER: Laboratory Biomarker Analysis

Correlative studies

OTHER: Pharmacological Study

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Objective response	Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (modified RECIST for pleural mesothelioma). Will be defined as a complete response or partial response on two consecutive occasions 4 weeks apart as determined by an independent radiologist. For each tumor group, the best response rate and its 95% exact confidence interval will be estimated using the Clopper and Pearson method. The combination treatment will be assessed by performing the independent binomial test comparing the best response rate versus the historical control for each tumor group. The Bayesian classification and information sharing method proposed by Lee and Chen may be applied.	Up to 4 years

Secondary Outcome Measures	Measure Description	Time Frame
Objective response	Will be assessed by immune-modified RECIST	Up to 4 years
Progression free survival	Will be assessed by RECIST 1.1 (modified RECIST for pleural mesothelioma). Will be estimated using Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model may be utilized to include multiple covariates in the time-to-event analysis.	The time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 4 years
Duration of response	Will be assessed by RECIST 1.1 (modified RECIST for pleural mesothelioma). For each tumor group the median duration of response and corresponding 2-sided 95% confidence interval will be reported.	The time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, assessed up to 4 years
Overall survival	Will be estimated using Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model may be utilized to include multiple covariates in the time-to-event analysis.	The time from enrollment to death from any cause, assessed up to 4 years
Progression free survival	Will be assessed by immune-modified RECIST	Up to 4 years
Duration of response	Will be assessed by immune-modified RECIST	Up to 4 years
Incidence of adverse events	Will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Verbatim adverse events and severity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The safety analyses will include all patients who received at least one dose of study treatment. Toxicity data will be summarized by frequency tables for each tumor type group. The association between the types and severity of toxicity and the tumor group will be evaluated. No formal statistical testing will be performed on these summary.	Up to 4 years
Change in targeted vital signs		Baseline up to 4 years
Change in targeted clinical laboratory test results		Baseline up to 4 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Signed informed consent form
Ability to comply with the study protocol, in the investigator's judgment
Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1; previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation; the pleural mesothelioma cohort will require measurable disease according to modified RECIST
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without granulocyte colony-stimulating factor support, obtained within 14 days prior to initiation of study treatment
Lymphocyte count >= 0.5 x 10^9/L, obtained within 14 days prior to initiation of study treatment
Platelet count >= 100 x 10^9/L without transfusion, obtained within 14 days prior to initiation of study treatment
White blood cell (WBC) count >= 2500/ul, obtained within 14 days prior to initiation of study treatment
Hemoglobin >= 90 g/L (patients may be transfused to meet this criterion), obtained within 14 days prior to initiation of study treatment
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =< 2.5 x upper limit of normal (ULN), obtained within 14 days prior to initiation of study treatment, with the following exceptions: patients with documented liver metastases: AST and ALT =< 5 x ULN; patients with documented liver or bone metastases: alkaline phosphatase (ALP) =< 5 x ULN
Serum bilirubin 1.5 x ULN, obtained within 14 days prior to initiation of study treatment
Serum creatinine =< 1.5 x ULN, obtained within 14 days prior to initiation of study treatment
Serum albumin >= 2.5 g/dL, obtained within 14 days prior to initiation of study treatment
For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN, obtained within 14 days prior to initiation of study treatment
For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment
A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus); examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices; the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
Appendiceal adenocarcinoma basket

Metastatic appendiceal adenocarcinoma
Not considered candidate for curative surgery
Nasopharyngeal carcinoma basket

Metastatic or locally recurrent disease not amenable to curative intent treatment
Any number of prior therapies, including 0
Human papilloma virus-associated cancers

Histologically proven squamous carcinoma of the anal canal, penile, vaginal, vulva, or refractory cervical cancer with progression or intolerance to at least one treatment regimen including cisplatin, oxaliplatin or carboplatin will be enrolled; human papilloma virus (HPV) confirmation is not required
Patients must have metastatic disease not amenable to surgical resection
If human immunodeficiency virus (HIV)+ positive, all patients infected with human immunodeficiency virus (HIV) and CD4+ T cell count > 400 cells/mm^3 may be eligible for study
Patients co-infected with hepatitis B virus and/or hepatitis C virus may be included in this study provided that their liver function tests remain within the limits listed above; patients must be followed by a hepatologist during the course of this study
Merkel cell carcinoma basket

Metastatic or locally recurrent disease not amenable to curative intent treatment
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Any number of prior therapies
Neuroendocrine tumors, pancreatic basket

Grade 1 or grade 2 (or described as low grade, intermediate grade, well differentiated, or moderately differentiated) according to reviewing pathologist
Progressive disease over the preceding 12 months
Any number of prior therapies, including 0
Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrollment
Neuroendocrine tumors, extrapancreatic basket

Grade 1 or grade 2 (or described as low grade, intermediate grade, well differentiated, or moderately differentiated; typical or atypical carcinoid if originating in lung) according to reviewing pathologist
Progressive disease over the preceding 12 months
Any number of prior therapies, including 0
Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrollment
Peritoneal mesothelioma basket

Refractory or intolerant to platinum and pemetrexed systemic therapy
Any number of prior therapies
Pleural mesothelioma basket

Metastatic or locally recurrent disease not amenable to curative intent treatment
Refractory to platinum and pemetrexed systemic therapy
Any number of prior therapies

Treatment for the studied cancer within 28 days prior to initiation of study treatment
Treatment with investigational therapy within 28 days prior to initiation of study treatment
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells
Known allergy or hypersensitivity to any component of the atezolizumab formulation
Known allergy or hypersensitivity to any component of the bevacizumab formulation
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions: patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study; patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study; patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

Rash must cover < 10% of body surface area
Disease is well controlled at baseline and requires only low-potency topical corticosteroids
No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; (history of radiation pneumonitis in the radiation field [fibrosis] is permitted)
Positive HIV test at screening (except in cohort 3, HPV-associated cancers)
Except in cohort 3, HPV-associated cancers, active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening; patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test and negative HBV deoxyribonucleic acid (DNA) test at screening, are eligible for the study
Except in cohort 3, HPV-associated cancers active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening; the HCV RNA test will be performed only for patients who have a positive HCV antibody test
Active tuberculosis
Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment; patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study, or up to 5 months following the anticipated last dose of atezolizumab
Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai stage 0)
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Except for cohort 4, Merkel cell carcinoma, prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is longer) prior to initiation of study treatment
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-· agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions: patients who received low-dose immunosuppressant medication are eligible for the study; patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
Pregnant or breastfeeding, or intending to become pregnant during the study; women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment
Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg); anti-hypertensive therapy to maintain a systolic blood pressure < 150 mmHg and/or diastolic blood pressure < 100 mmHg is permitted
Prior history of hypertensive crisis or hypertensive encephalopathy
History of stroke or transient ischemic attack within 6 months prior to cycle 1, day 1
Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to cycle 1, day 1
Patients with a baseline electrocardiography (ECG) demonstrating a corrected QT (QTc) > 460 ms
Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence of therapeutic anticoagulation)
Current or recent (within 10 calendar days prior to cycle 1, day 1) use of dipyramidole, ticlopidine, clopidogrel, or cilostazol
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 calendar days prior to the first dose of bevacizumab
History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to cycle 1, day 1
Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection; all patients with >= 2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein
Appendiceal adenocarcinoma basket

Complete or partial bowel obstruction
Epstein-Barr virus-associated nasopharyngeal carcinoma basket:

None
Human papilloma virus-associated cancers basket

None
Merkel cell carcinoma basket:

None
Neuroendocrine tumors, pancreatic basket:

Grade 3, poorly differentiated neuroendocrine carcinoma
Large cell or small cell histology
Neuroendocrine tumors, extrapancreatic basket:

Grade 3, poorly differentiated neuroendocrine carcinoma
Large cell or small cell histology
Peritoneal mesothelioma basket:

None
Pleural mesothelioma basket:

None

Collaborators and Investigators

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